Purpose <p>To report the pain relief and procedure-related outcomes of percutaneous cryoablation (CA) of painful endometriosis deposits in unusual anatomic locations.</p> Materials and Methods <p>A retrospective search of institutional radiological information system identified a total of 15 patients (median age 35.5&#xa0;years; interquartile ranges—IQR 33–38). Patients and lesions specific data as well as procedural and follow-up information were collected, analyzed, and presented using descriptive statistical methods.</p> Results <p>A total of 16 painful target lesions situated in the umbilicus (7/16; 43.8%), diaphragm (4/16; 25.0%), inguinal canal (3/16; 18.8%), and within the muscular layers of the uterus (i.e., adenomyosis; 2/16; 12.4%) underwent CA. The median of the largest diameter of the target lesions was 19&#xa0;mm (IQR 13–22.3). Primary and secondary rates of complete pain relief were achieved in 86.7% (13/15 patients) and 93.3% (14/15 patients; one patient receiving additional CA for recurring pain) of patients, respectively. Each lesion underwent one single intervention, thus accounting for a total of 16 CA procedures. Eleven interventions were carried out under general anesthesia (11/16; 68.8%), with combination of ultrasound and cross-sectional imaging (CT or MRI) being the most used modality for image guidance (10/16; 62.5%). Nearly all interventions (15/16; 93.8%) required adjunctive protective measures with hydrodissection (13/16; 81.3%) and combination of hydrodissection and cutaneous protection with warm saline filled gloves (9/16; 56.3%) being the two most common protective measures. Two (2/16; 12.5%) complications were noted.</p> Conclusions <p>Percutaneous CA of painful endometriosis deposits in unusual anatomic locations seems highly effective and safe.</p> Graphical Abstract <p></p>